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January2005 Vol.42 Issue:      1 Table of Contents
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Role of Sympathetic Nervous System Dysfunction in Alopecia Areata

Ahmed Azab1, Magdy El-Sohafy2, Ahmed Abd EI-Khabir2, Ahmed Abo-Eleneen3
Departments of Neurology1, Dermatology & Andrology2, Mansoura University, Clinical Pathology, Tanta University3

ABSTRACT

Thirty patients with alopecia areata (AA) and ten normal controls were included in the present study. The patients were classified into 3 groups; 20 patient with localized alopecia areata (LAA), 6 patients with alopecia totalis (AT) and 4 patients with alopecia universalis(AU). Sympathetic skin response (SSR) recording as a test for autonomic nervous system function were done for patients and controls. There were no statistically significant differences in latency and amplitude between patients and controls indicating that AA did not have a significant effect on SSR. Also, there were no significant differences between different groups of patients and controls as regard blood pressure and heart rate. The role of catecholamines as neurotransmitters related to stress was assessed by measuring blood levels of noradrenaline (NA) and dopamine b hydroxylase (D b H). A statistically moderately significant increases in the mean blood levels of NA and DbH were found in patients with AT and AU. However, a non-significant increase in the mean blood NA level and a mildly significant increase in the mean blood DbH level were found in patients with LAA as compared to controls. In conclusion, AA did not have a significant effect on SSR. However, to exclude any autonomic dysfunction, other tests for complete evaluation of autonomic NS should be evaluated in a future study. Also, liability in catecholamines secretion could have a role in pathogenesis of AA or in determination of its clinical pattern, though; the effect of stress as a result of the disease on catecholamines secretion should be considered.

(Egypt J. Neurol. Psychiat. Neurosurg., 2005, 42(1): 1-7).




 

INTRODUCTION

 

Nervous system (NS) plays a significant role in certain dermatoses as psoriasis1, atopic dermatitis2 and vitiligo3, by exerting effect on immune cells through neuro-transmitters. Hence, the concept of neuroimmunocutaneous system (NICS) was suggested4.

Recently, much evidences suggest that alopecia areata (AA) is a tissue restricted T-lymphocytes mediated autoimmunc disease5. Stress may be an important precipitating factor in some cases of AA. Moreover, marked correlation between psychological factors and the activity of adrenergic sympathetic nervous system was proved in patients with AA6.

Sympathetic skin response (SSR) is one of the tests that was used to assess the sympathetic nervous system (SNS) functions, though data regarding SSR in immunologically mediated skin disorders are few7.

The objective of this study was to assess SSR in patients with AA (not reported before). Also the role of catecholamines as neurotransmitters related to stress will be assessed by measuring blood levels of noradrenaline (NA) and dopamine B hydroxylase (DbH), as a catecholalfine synthesizing enzyme, in patients with different clinical patterns of AA.

SUBJECTS AND METHODS

 

The present study involved thirty patients with AA recruited from Dermatology out patient clinic of Mansoura University Hospital, together with ten healthy age, sex and height matched controls, since SSR latency correlated well with the subject height8. Subjects with peripheral neuropathy or those having a history of sudomotor and/or vasomotor impairment were excluded. Also, none of the subjects were taking any medications or had any disease that could affect SNS.

Patients were divided into 3 groups according to the clinical pattern ofAA:

-        Localized alopecia areata (LAA): 20 patients.

-        Alopecia totalis (AT): 6 patients.

-        Alopecia universal is (AU): 4 patients.

To minimize stress as a result of the disease, AA should be stable for at least 6 months before the study.

Blood pressure and heart rate were determined for each subject. Moreover J routine blood chemistry, urine analysis and CBC were done and found to be normal in all subjects.

 

Samples collection:

Two ml blood was collected from each subject into EDTA tube (l mg/ml blood). Plasma were separated and stored frozen at -20°C till analysis of plasma noradrenaline by ELISA. The material was supplied by IBL (Hamborg).

Another 2 ml blood samples were collected into plain tubes. Serum were separated and stored frozen at -200 C till analysis for determination ofDbH. The material supplied by Neuro-Biotech. Inc. (Canada) using the sympath. TM 25 enzymatic assay principle depending upon conversion of tyramine in the presence of DbH to octopamine which is derived to p-hydroxy-benzaldhyde by periodate cleavage.

 

SSR recording9:

While the subject in relaxed and supine position in a semi dark room at ambient temperature of 25°C, SSR recordings were performed by a Medelec Premiere electromyograph. A 6 mm diameter stainless steel disk electrodes was used. The active electrode was attached to the palm, and the reference electrode was attached to the dorsum of the hand bilaterally. Band pass filters were~ between 1 and 1000 Hz and the sensitivity was set between 0.5 and 1 mv. SSR recordings were obtained from both hands using 2 channels after one pulse. Pulses in 0.1 ms duration and 30 mA intensity were applied to the skin of both wrists exciting nervus medianus. The latency from the onset of the stimulus artifact to the onset of the skin response, and amplitude from peak to peak measurement in SSR were performed manually.

The mean values of the parameters were derived from 4 SSR recordings.

 

Statistical analysis:

Using Statistical Package for Social Sciences (SPSS) for Microsoft Windows, the results were analyzed using student" t " test

 

RESULTS

 

A summary of the clinical data of the patients and controls is presented in Table (1). The ages of the patients ranged from 14 to 43 years (25.9±6.9) while, in control group it ranged from 17 to 45 years. Duration of the disease ranged from 6 to 36 months (17.7±12.4). There were no statistically significant differences as regard sex. age, height, blood pressure and heart rate (HR) parameters between patients and controls.

The mean values for latency and amplitude in SSR recording were presented in Table (2). There were no significant differences in these values between patients and control groups.

The mean blood levels of NA and DbH for AA patients and control groups were presented in Table (3) The mean blood levels ofNA showed a statistically significant increase in patients with AT and AU compared to control group. Moreover, a statistically significant increase in the mean levels of DbH was found in the 3 groups of patients in relation to control group.


Table 1. Clinical data of AA patients and controls.

 

 

LAA

n=20

AT

n=6

AU

N=4

Total

N=30

Controls

N=10

Sex

 

 

 

 

 

    Males

12 (60%)

4(66.7%)

2 (50%)

18 (60%)

6 (60%)

    Females

8 (40%)

2 (33.3%)

2 (50%)

12 (40%)

4 (40%)

Age (years)

    Mean±S.D.

26.7±8.2

27±5.6

22.3±4.8

25.9±6.9

24.7±9.6

Height (cm)

 

 

 

 

 

    Mean±S.D.

165.6±14.1

164.3±12.7

157.2±13.3

162.4±14.5

164.7±13.7

Blood pressure

 

 

 

 

 

    Systolic

111.4±11.5

113.6±9.7

115.2±10.1

112.8±1.8

109.5±8.5

    Diastolic

77.2±7.3

76.7±6.1

75.5±6.4

76.9±7.5

74.6±6.7

Heart rate

75.2±5.1

74.8±4.3

76.2±6.4

75.5±6.5

74.6±5.7

 

Table 2. Results of SSR in patients groups versus controls.

 

 

LAA

n=20

AT

n=6

AU

N=4

Total

N=30

Controls

N=10

Latency (sec)

   Mean

   SD

   t test

 

1.50

0.21

0.38

 

1.48

0.15

0.71

 

1.47

0.17

0.75

 

1.49

0.18

0.67

 

1.53

0.1

Amplitude(mv)

   Mean

   SD

   t test

 

4.65

2.37

0.35

 

4.74

2.15

0.3

 

4.72

1.98

0.6

 

4.69

2.10

0.48

 

4.31

2.45

t non significant (p>0.05)

 

Table 3. Blood levels of NA and DbH in patients groups versus controls.

 

 

LAA

n=20

AT

n=6

AU

N=4

Total

N=30

Controls

N=10

NA

   Range

   Mean

   SD

   t test

 

166-645

408.2

136

1.29

 

450-600

505.8

79.4

3.34*

 

450-630

537.5

86.2

2.64*

 

166-645

448.5

130.5

2.27*

 

150-597

339.9

139.8

DbH

   Range

   Mean

   SD

   t test

 

27.4-45.6

38.2

5.8

3.33*

 

39.7-42

41.1

3.1

4.24**

 

39.8-45.9

41.6

3.7

3.56**

 

27.4-45.9

39.8

4.6

5.11**

 

25-42

30.8

5.6

* t significant at p £ 0.05

* t significant at p £ 0.01

 

Fig. (1): Sympathetic skin response (SSR) recording in a patient with AA.

 

 


DISCUSSION

 

The nervous system, immune system and skin (NICS) are closely linked both anatomically and physiologically, and use the same language of cytokines and neurotransmitters4. Neurons come in contact with cutaneous cells by way of axon terminals containing neurosecretory vesicles. Both Langerhan's cells (antigen presenting cells) 10 and dermal dendritic cells11 are in contact with these axons.

During the course of some skin disorders, NICS is destabilized. Also, immune cells transiently present in the skin (e.g. macrophages and lymphocytes) are modulated by cutaneous neuromediators, including catecholamines, through receptors4.

The contribution of SNS function to the genesis of AA was confirmed by Sergeev et al.12. They found that 10-12 sessions of sinusoidal modulated currents in the area of cervical sympathetic node area was an effective physiotherapeutic modality in AA treatment.

SSR is one of the indices of peripheral nerve function. Using an electrical stimulus, the afferent fibers of the reflex are cutaneous sensory fibers. It has a common efferent pathway through the spinal cord, pre- and post-ganglionic sympathetic fibers and sweat glands as effectors13.

Abnormal SSR were reported in leprosy14, scleroderma15 and palmoplanter hyper-hidrosis16. Moreover, SSR were investigated in some immunologically mediated skin diseases as vitiligo and psoriasis17,7. AA may extensively affect the skin and autoimmunity was implicated in its pathogenesis (as vitiligo and psoriasis), however, SSR recording in AA was not reported before. In our study, SSR could be obtained from every patient studied without a statistically significant differences in latency an amplitude as related to controls indicating that AA did not have a significant effect on SSR. However, in the diagnosis of autonomic NS dysfunction, SSR needs to be taken into account with clinical symptoms and other tests for complete evaluation of autonomic NS function.7

Emotional stress is one of the most powerful precipitating factor in AA. Up to 29% of patients with AA were found to have psychological factors and family situations that may affect the onset and the course of the disease18, however, the pathomechanism whereby psychological factors precipitate the disease is totally unknown.

Production of AA based on mental motive theory19 was confirmed by Puchalski6, who found that high level of activity, emotional unstableness as well as tendencies to neurotic activities are connected with a statistically significant variation in urinary catecholamines (adrenaline, noradrenaline and dopamine) secretions. He suggested that this liability of catecholamine secretion is. the cause of this functional disorder.

In our study, no significant differences were found between different groups of AA and controls as regard blood pressure and heart rate. However, the mean blood level of NA and DbH showed a statistically moderately significant increases in patients with AT & AU (p<0.01). In patients with LAA, there was a non significant increase in the mean blood level ofNA and a statistically mild significant increase in the mean level ofDf3H as compared to controls (p<0.05).

The above mentioned findings could be explained by the fact that patients with AA perceive certain challenging situation as more stressful than do controls and react accordingly in a different psychoendocrine pattern. However, the increase in catecholamines secretion due to stress as a result of the disease (AA) itself could not be excluded.

Also, as the increases in blood NA and DbH levels were more statistically significant in patients with AT and AU as compared to those with LAA, this liability in catecholamines secretions could have a role in determining the pattern of AA. However, extensive AA could be a more stressful condition than localized AA with a more catecholamine secretion.

We could not found, in the literature, any report regarding the levels of these parameters in AA, however, in a disease like psoriasis with a postulat~d disorder in NICS7, a significant increase in concentration of circulating noradrenaline together with a slight differences in adrenaline and dopamine blood levels in relation to controls were reported20. Also, in vitiligo, it has been reported that noradrenaline and adrenaline biosynthesis in keratinocytes of the diseased area was increased21.

In conclusion, our result did not indicate any effect of AA on SSR recordings, though it is just one of the tests which was used for assessment of SNS function. Also, the significant increase in noradrenaline and DbH blood levels in patients with AA could be implicated in pathogenesis of AA. However, further study regarding catecholamine biosynthesis in the affected skin could be more informative.

 

REEFRENCES

 

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